Gabapentin is a pharmacological agent that mimics the effects of GABA (γ-aminobutyric acid), but gabapentin does not appear to bind a GABA receptor (e.g., GABAA and GABAB receptors) or have an effect on GABA uptake. Gabapentin has been found to interact with the alpha-2-delta (β2δ) subunit of voltage-gated calcium channels. Many of the pharmacological effects of gabapentin may be due to its interaction with voltage-gated calcium channels. It is believed that gabapentin decreases calcium ion flow into a neuron, rendering the neuron less excitable. Inhibition of presynaptic calcium influx may prevent the release of neurotransmitters. Thus, like GABA, gabapentin can dampen overactive neural circuitry.
Solid formulations of gabapentin, such as NEURONTIN, are currently available for oral administration. Oral gabapentin has been primarily used to treat epilepsy although it has been used off-label to treat neuropathic pain and has recently received an FDA-approval for the treatment of one type of neuropathic pain, post-herpetic neuralgia. Some gabapentin can access the CNS when administered orally, because gabapentin is transported across the gut and the blood-brain barrier. It is believed that gabapentin is transported across the blood-brain barrier via an active and saturable L-amino acid transporter. Thus, the amount of gabapentin reaching CNS sites of action is limited. Because this transporter is saturable, even if the concentration of gabapentin in the plasma is increased, the amount which crosses the blood-brain barrier will remain constant.
Solutions of gabapentin have been prepared extemporaneously for direct administration to the CNS in preclinical animal studies. In some studies, such solutions have been administered intrathecally as a single bolus or as multiple boluses. However, the administration of a solution to the CNS presents many concerns, including the threat of serious infection. While such concerns are not of considerable importance in preclinical animal studies, they are of paramount importance in the context of administration to humans.
Accordingly, the sterility of a solution comprising gabapentin, which solution is to be administered to the CNS, cannot be taken lightly. Typically, solutions are sterilized either by heat or filtration. In the case of solutions containing gabapentin, a sterilization process involving heat would generally be considered undesirable. This is because heat would be expected to result in decreased stability of gabapentin and increased production of gabapentin lactam, having a chemical structure of formula (I):

According to U.S. Pat. No. 6,054,482, “The lactams display a certain toxicity and must, therefore, be avoided as far as possible. For example, gabapentin has a toxicity (LD50, mouse) of more than 8000 mg/kg, for the corresponding lactam (VI) a toxicity of 300 mg/kg.” Column 4, lines 50–53. As a sterilization process involving heat may result in increased levels of the gabapentin lactam, heating of solutions prior to administration to the CNS of a patient would have been inadvisable.